The scope of this proposed research includes an in depth study of the nature of hyperthermic damage on cells in vitro and in vivo. In particular, studies will be made on the biochemical nature of types I and II thermotolerance. Attempts will then be made to extend evidence from in vitro studies to the degree and duration of thermotolerance on several normal tissues (skin and spinal cord) and also for a single model transplantable tumor in the rat. Also, investigation of the dose modifying effect of oxygen on both hyperthermic cell killing and hyperthermia plus x-irradiation in both asynchronous an synchronized cell populations will be made.